EXCHANGE 


INVESTIGATION  OF 
BROMONITROCAMPHANE 


BY 

PAUL  MEADB  GINNINGS 

B.S.   University  of  Illinois,  1919 
M.S.  University  of  Illinois,  1920 


THESIvS 

SUBMITTED  IN  PARTIAL  FULFILLMENT  OF  THE  REQUIREMENT 

FOR  THE  DEGREE  OF  DOCTOR  OF  PHILOSOPHY  IN  CHEMISTRY 

IN  THE  GRADUATE  SCHOOL  OF  THE  UNIVERSITY  OF 

ILLINOIS,  1922. 


'Reprinted  from  the  JOURNAL  OF  THE  AMERICAN  CHEMICAL  SOCIETY, 
Vol.  XLIV.  No.  11.       November,  1922.] 


INVESTIGATION  OF 
BROMONITROCAMPHANE 


BY 

PAUL  MEADE  GINNINGS 

B.S.  University  of  Illinois,  1919 
M.S.  University  of  Illinois,  1920 


THESIS 

SUBMITTED   IN   PARTIAL  FULFILLMENT  OF  THE  REQUIREMENT 

FOR  THE  DEGREE  OF  DOCTOR  OF  PHILOSOPHY  IN  CHEMISTRY 

IN  THE  GRADUATE  SCHOOL  OF  THE  UNIVERSITY  OF 

ILLINOIS,  1922. 


[Reprinted  from  the  JOURNAL  OP  THE  AMERICAN  CHEMICAL  SOOIKTY, 
Vol.  XLIV,  No.  11.       November,  1922.] 


ACKNOWLEDGMENT 

The  author  wishes  to  take  this  opportunity  to  express  his  indebtedness 
to  Prof.  W.  A.  Noyes,  upon  whose  suggestion  this  investigation  was  under- 
taken, and  under  whose  kind  direction  it  was  carried  out. 


INVESTIGATION  OF  BROMONITROCAMPHANE1 

About  20  years  ago  Forster1  discovered  that  when  potassium  hypobro- 
mite  is  allowed  to  act  on  camphoroxime,  a  bromonitro  compound  is  ob- 
tained which  he  named  bromonitrocamphane  and  to  which  he  assigned 
the  structure  I. 


CH, 


CH, 


CH, 


%-• 

[a— C— C 


-NO2 


H3 


CH 


CH; 


CH2  -  CH- 

I 

He  and  his  collaborators  established  fairly  conclusively  the  main  points 

1  Forster,  J.  Chem.  Soc.,  71,  199  (1897);  71,  1030  (1897);  75,  1141  (1899);  77,  251 
(1900);  79,  108  (1901);  79,  264  (1901);  79,  644  (1901);  Ref.  4;  79,  987  (1901);  79,  1003 
(1901);  81,  865  (1902);  83,  78  (1903)  ;  Proc.,  28,  313  (1912). 


.-".';••  ,;:,:  ""..:/.*  .  } 

6 

of  interest,  but  there  were  two  things  not  accomplished.  One  is  the 
oxidation  of  bromonitrocamphane  and  identification  of  the  products, 
and  the  other,  proof  that  the  bromonitrocamphane  anhydride  (II)  con- 
tained the  carbonyl  group  in  its  molecule.  In  view  of  the  above  facts, 
it  seemed  desirable  to  investigate  further  the  above  compounds. 

When  bromonitrocamphane  is  treated  with  alcoholic  silver  nitrate,  it 
loses  the  elements  of  hydrogen  bromide  and  forms  Compound  III  with 
the  bridge  or  trimethylene  ring  in  the  molecule.  This  can  be  taken  by 
several  steps  to  an  isomer  of  camphor  which  has  the  nitro  group  in  III 
replaced  by  an  hydroxy  group. 


CH3 


.C-NOZ  CHZ 


V 

CH3-C-CH3 


CH3-C-CH3 


m  N 

When  bromonitrocamphane  is  treated  with  cone,  sulfuric  acid  in  the  cold, 
it  loses  the  elements  of  water  to  form  the  anhydride,  which  is  easily  con- 
verted into  an  isomer.  This  anhydride  and  its  isomer  are  changed  very 
easily  into  an  unsaturated  nitrile  (IV)  and  this  nitrile  can  be  hydrolyzed 
to  the  corresponding  unsaturated  acid,  named  infra-campholenic  acid 
by  Forster. 

Oxidation  of  bromonitrocamphane  was  tried  out  some  time  ago2  but 
under  the  conditions  of  the  oxidation,  no  camphoric  acid  or  camphoronic 
acid  was  obtained.  These  should  be  the  products  of  the  oxidation  if  the 
bromine  and  nitro  groups  are  situated  in  the  — CO — CH2 —  side  of  the 
camphor  molecule.  The  oxidation  has,  however,  been  repeated  in  this 
investigation  under  more  varying  conditions  and  camphor,  camphoric 
acid,  camphoronic  acid  isolated  from  the  products  of  the  oxidation. 

The  formation  of  bromonitrocamphane  by  the  action  of  potassium  hy- 
pobromite  on  camphbroxime  is  rather  unusual.  Evidently,  the  synthesis 
involves  both  bromination  and  oxidation.  In  his  original  work  on  this 
compound  Forster  thought  that  the  mechanism  of  the  reaction  was  bro- 
mination to  bromonitrosocamphane,  and  then  oxidation  to  the  bromonitro- 
camphane. He  noticed  that  a  green  compound  was  formed  during  the  syn- 
thesis and  he  suggested  that  this  was  a  hydrate  of  bromonitrocamphane, 
since  it  gave  bromonitrocamphane  on  exposure  to  air,  or  on  drying.  The 
mechanism  of  the  synthesis  has  been  investigated  in  detail  in  this  paper. 
The  results  indicate  that  the  mechanism  is  partially  as  Forster  thought, 

2  Gwinn,  Thesis,  University  of  Illinois,  1920. 


that  is  bromination  and  then  oxidation,  but  that  no  hydrate  of  bromo- 
nitrocamphane  is  formed.  It  has  been  found  that  the  green  color  is  due 
to  a  product  of  a  side  reaction,  hydroxy-nitrosocamphane.  This  is  due 
to  the  fact  that  potassium  hypobromite  can  act  either  as  an  oxidizing 
agent  or  as  a  brominating  agent  and  it  usually  does  both  when  it  is  allowed 
to  act  on  camphoroxime.  The  course  to  bromonitrocamphane  is  fol- 
lowed to  the  larger  extent,  but  some  of  the  hydroxy-nitrosocamphane 
is  almost  always  present  in  the  final  product. 

The  question  as  to  the  correct  structural  formula  of  the  anhydride 
formed  by  the  action  of  cone,  sulfuric  acid  on  bromonitro-camphane 
has  not  been  satisfactorily  answered.  Empirically,  the  reaction  involves 
simply  the  removal  of  the  elements  of  water  to  form  the  anhydride  but, 
as  Forster  said,  owing  to  the  fact  that  a  nitro  group  is  involved  in  the 
dehydration,  it  is  difficult  to  ascribe  a  structural  formula  to  the  product. 
From  the  fact3  that  2-bromo-l-nitrocamphane  as  shown  below  in  For- 
mula I  does  not  yield  an  anhydride,  it  would  seem  that  both  of  the  hy- 
drogens on  that  carbon  atom  are  involved  in  the  dehydration.  But  the 
bromine  atom  exerts  some  influence  because  ordinary  nitrocamphane  does 
not  give  an  anhydride  when  treated  with  cone,  sulfuric  acid.  On  first 
thought,  it  would  be  expected  that  Formula  II  would  'represent  the  cor- 
rect structure  of  the  anhydride. 

H  Br  Br 

C—  NO2 


/—       2  /v 

C8H14<J  C8H14<(|\N=0         C8H1 

\CHBr  XX 


I  II  III 

It  was  found,  however,  by  Forster  that  dil.  mineral  acids  and  other  milder 
reagents  such  as  hydroxylamine  convert  the  anhydride  into  an  isomer 
which  gives  a  benzoyl  derivative. 

Of  course  Formula  II  is  not  the  only  formula  that  can  be  ascribed  to 
the  first  anhydride.  Very  pertinent  to  this  question  is  the  work  of  Wallach4 
on  the  action  of  sulfuric  acid  on  various  oximes.  He  has  shown  that  in 
many  cases  the  first  step  in  the  reaction  is  the  rearrangement  of  the  oxime 
to  the  lactam  compound.  Following  a  similar  line  of  reasoning,  the 
oxygen  atoms  of  the  nitro  group  might  be  thought  to  rearrange  on  to  the 
adjacent  carbon  atom  thus  forming  two  hydroxyl  groups,  and  the  nitro- 
gen atom  might  assume  a  position  between  the  two  carbons.  Then, 
of  course,  the  sulfuric  acid  would  remove  the  elements  of  water  leaving 
the  carbonyl  group  in  the  molecule,  as  in  Formula  III  above.  Assuming 
this  to  be  the  structure  of  the  first  anhydride,  it  is  probable  that  the 
second  form  of  the  anhydride,  an  isomer,  could  be  represented  as  the  enol 
form  as  follows. 

3  Forster,  /.  Chem.  Soc.,  79,  653  (1901). 

4  Wallach,  Ann.,  309,  1  (1899);  312,  171  (1900). 


Br  Br 


/    \N 

\C=0 


If  the  carbonyl  group  is  present  in  the  first  anhydride,  then  it  should  give 
the  regular  carbonyl  reactions.  But  Forster,  in  working  on  the  struc- 
ture of  the  anhydride,  found  that  the  first  isomeric  anhydride  gave  an 
hydroxylamino  compound  with  hydroxylamine,  instead  of  the  oxime 
which  would  be  the  derivative  expected.  He  was  unable  to  cause  the 
carbonyl  group  to  react  as  such.  In  carrying  out  this  investigation, 
recently,  it  seemed  that  treatment  of  the  first  isomeric  anhydride  with 
methyl  magnesium  iodide  in  the  regular  Grignard  reaction  might  shed 
some  light  on  the  structure  of  the  compound.  This  has  been  done  in 
this  work  and  it  is  believed  that  the  results  obtained  furnish  convincing 
evidence  that  the  structure  of  the  first  isomeric  anhydride  is  that  which 
represents  it  as  a  substituted  inner  amide.  This  was  originally  proposed 
by  Forster,  but  he  was  unable  to  demonstrate  the  presence  of  the  carbonyl 
group,  probably  because  of  the  fact  that  the  Grignard  reaction  was  not  in 
such  general  use  then  as  it  is  at  the  present  time. 

When  the  first  isomeric  anhydride  is  treated  with  methyl  magnesium 
iodide  according  to  the  regular  Grignard  reaction,  and  the  product  de- 
composed with  water,  a  new  compound  is  obtained  which  has  its  molecu- 
lar weight  increased  by  1  carbon  atom  and  4  hydrogen  atoms.  This  com- 
pound gives  a  benzoyl  derivative  by  the  Schotten-Baumann  reaction, 
and  the  derivative  has  one  benzoyl  group.  When  the  compound  pro- 
duced by  the  Grignard  reaction  is  treated  with  alcoholic  potash,  the 
bromine  atom  is  lost,  the  nitrogen  atom  is  eliminated  as  ammonia,  and 
a  methyl  ketonic  acid  obtained  whose  melting  point  checks  with  that 
acid  which  would  be  obtained  theoretically  in  this  reaction.5  The  changes 
that  take  place  from  the  first  isomeric  anhydride  would  then  be  repre- 
sented as  follows. 

Br  Bt-  ^  COOH 


This  furnishes  even  greater  confirmatory  evidence  for  the  inner  substituted 
amide  formula  for  the  first  form  of  the  bromonitrocamphane  anhydride. 
In  other  words,  it  completes  the  proof  for  this  structural  formula  for 
the  first  isomer  of  bromonitrocamphane  anhydride  and  supplements 
Forster' s  data  for  the  isomeric  compound,  the  enol  form  for  this  same 
anhydride. 

6  Winzer,  Ann.,  257,  311  (1800). 


9 

Experimental 

Preparation  of  Bromonitrocamphane. — The  method  employed  is  essentially  the  same 
as  used  by  Forster  originally,  except  that  a  larger  quantity  of  bromine  is  added  to  the  re- 
action mixture.  By  using  a  solution  of  potassium  hypobromite  in  which  there  is  a  slight 
excess  of  bromine,  it  has  been  found  that  the  product  comes  out  almost  pure  with  very 
little  formation  of  the  hydroxy-nitrosocamphane,  the  green  compound.  The  weights 
used  were  600  g.  of  bromine,  600  g.  of  potassium  hydroxide,  100  g.  of  camphoroxime. 

Oxidation  of  Bromonitrocamphane  with  Nitric  Acid. — In  this  experiment,  25  g. 
of  bromonitrocamphane  was  oxidized  with  a  nitric  acid  solution  (200  cc.  of  water  to 
300  cc.  of  cone,  nitric  acid).  The  mixture  was  refluxed  for  a  week,  day  and  night,  and  at 
the  end  of  the  time,  the  camphoronic  acid  separated  as  the  barium  salt  of  the  acid  and  the 
camphoric  acid  as  the  anhydride.  If  the  same  type  of  oxidation  is  conducted,  except  for 
a  shorter  time,  it  is  possible  to  condense  considerable  quantities  of  camphor  in  the  con- 
denser tube,  showing  the  successive  steps  in  the  oxidation  of  bromonitrocam- 
phane. 

Quantitative  Observations  on  the  Course  of  the  Action  of  Potassium  Hypobromite 
on  Camphoroxhne. — Working  on  the  theory  that,  possibly,  an  intermediate  bromo- 
nitroso  compound  might  be  formed  with  an  appreciable  lag  in  the  reaction,  and  that 
accordingly  there  might  be  a  definite  variation  or  break  in  the  curve  of  the  utilization  of 
the  potassium  hypobromite,  the  following  set  of  experiments  was  run  to  determine 
whether  any  sharp  variation  took  place  in  the  action  of  the  potassium  hypobromite. 

Quantitative  amounts  of  camphoroxime  (6.70  g.  or  0.04  mol.),  bromine  (10.50  g. 
or  0.06  mol.),  and  potassium  hydroxide  (20  g.  in  200  cc.  of  water  or  0.35  mol.),  were 
caused  to  react  while  the  mixture  was  vigorously  stirred.  By  the  removal  of  aliquot 
parts  of  the  potassium  hypobromite,  addition  to  potassium  iodide,  and  titration  of  the 
liberated  iodine  with  standard  sodium  thiosulfate  solution,  with  starch  as  an  indicator, 
it  was  possible  to  get  a  relation  between  the  grams  of  bromine  used  per  unit  time. 
This,  plotted,  showed  that  there  was  no  definite  break  in  the  curve  of  the  utilization  of 
the  bromine. 


Time      Bromine  used    Time     Bromine  used     Time     Bromine  used 

Hrs. 

G. 

Hrs. 

G. 

Hrs. 

G. 

0.25 

6.42 

1.50 

9.00 

3.00 

10.05 

0.50 

7.27 

2.00 

9.35 

4.00 

10.48 

1.00 

8.58 

.  , 

,  t 

t  , 

•  • 

Preparation  of  Bromonitrocamphane  Anhydride  (Forster's).— The  method  given 
here  is  modified  so  that  the  reaction  can  be  kept  under  control.  Forster  originally  added 
the  solid  bromonitrocamphane  directly  to  the  cone,  sulfuric  acid  with  the  result  that, 
since  the  reaction  is  exothermic,  considerable  decomposition  took  place  and  small  yields 
of  the  anhydride  were  obtained.  His  method  has  been  modified  by  dissolving  the  bromo- 
nitrocamphane in  low-boiling  petroleum  ether,  and  allowing  this  to  drip  slowly,  into  a  cold 
mixture  ( — 10°)  of  cone,  sulfuric  acid  and  petroleum  ether  which  was  stirred  vigorously. 
The  bromonitrocamphane  is  taken  over  quickly  by  the  sulfuric  acid,  but  when  the 
temperature  is  kept  below  — 5°  the  yield  of  the  anhydride  is  almost  quantitative  and  the 
product  is  almost  pure  white,  scarcely  requiring  recrystallization.  The  anhydride  is 
obtained  finally  by  allowing  the  cone,  acid  solution  to  drip  over  finely  crushed  ice,  where- 
by the  anhydride  is  precipitated  as  a  slightly  yellow,  flocculent  solid.  This  is  usually  pure 
enough  for  most  purposes,  but  it  can  be  recrystallized  from  hot  alcohol  to  obtain  it  in 
pure  condition. 

Action  of  the  Grignard  Reagent  (Methyl  Magnesium  Iodide)  on  Bromonitro- 
camphane Anhydride. — Five  g.  of  magnesium  turnings  is  immersed  in  200  cc.  of  dry 


10 

ether  in  a  1 -liter  flask  connected  to  a  reflux  condenser  with  air-tight  connections.  A  small 
amount  of  iodine  is  introduced  as  a  catalyst  and  20  g.  of  methyl  iodide  is  added  in  por- 
tions, so  that  the  vigorous  reaction  is  well  under  control.  The  solution  is  refluxed  until 
all  action  has  ceased  and  there  is  only  a  very  small  amount  of  magnesium  left  in  the 
bottom  of  the  flask.  Then  10  g.  of  the  bromonitrocamphane  anhydride,  dissolved  in 
about  50  cc.  of  dry  ether,  is  added  in  small  portions  through  the  top  of  the  condenser  and 
this  mixture  refluxed  for  several  hours.  The  flask  is  then  disconnected,  and  small 
amounts  of  water  added  cautiously  to  decompose  the  Grignard  compound.  After  the 
main  reaction  has  ceased,  some  dil.  sulfuric  acid  is  added.  The  whole  is  stirred  well, 
at  least  for  several  minutes  and  the  ether  separated  by  means  of  a  separatory  funnel, 
washed  with  water,  with  a  solution  of  sodium  carbonate,  again  with  water  several  times, 
dried  over  calcium  chloride  and  evaporated  almost  to  dryness  over  the  steam-bath. 
At  this  point,  if  the  liquid  residue  is  allowed  to  cool  slowly  so  that  the  last  portion  of  the 
ether  evaporates  spontaneously,  the  derivative  crystallizes  in  large,  lustrous,  transparent 
plates,  m.  p.  117-8°.  It  is  insoluble  in  acids  or  alkalies,  is  soluble  in  ether  or  alcohol,  but 
insoluble  in  water.  It  is  converted  readily  into  the  corresponding  acyl  derivatives. 

Analysis.  Subs.,  0.1705:  AgBr,  0.1230  (Br,  0.0524).  Calc.  for  CnH18ONBr; 
Br,  30.75.  Found:  30.73. 

Analysis  of  the  Benzoyl  Derivatives  of  Methyl  Bromonitrocamphane  Anhydride. — 
By  treating  the  methyl  bromonitrocamphane  anhydride  with  benzoyl  chloride  according 
to  the  Schotten-Baumann  reaction,  a  benzoyl  derivative  is  obtained,  fine  white  crystals 
crystallized  from  hot  dil.  alcohol,  m.  p.  113-114°.  It  will  also  crystallize  from  ether  in 
star-shaped  needle  groups. 

Analysis.  Subs.,  0.2141:  AgBr,  0.1094.  Calc.  for  C18H22O2NBr:  Br,  21.90. 
Found:  21.75. 

Action  of  Alcoholic  Sodium  Hydroxide  on  Methyl  Bromonitrocamphane  Anhy- 
dride. Formation  of  Aceto-camphenyl  Carboxylic  Acid. — To  observe  the  action  of 
alcoholic  sodium  hydroxide  on  the  compound  produced  by  the  action  of  methyl  mag- 
nesium iodide,  which  is  named  methyl  bromonitrocamphane  anhydride,  5  g.  of  this 
derivative  was  dissolved  in  25  cc.  of  ethyl  alcohol,  10  cc.  of  cone,  sodium  hydroxide 
solution  was  added  and  the  mixture  or  solution  boiled  for  a  few  minutes.  A  strip  of 
moistened  red  litmus  suspended  in  the  vapors  issuing  from  the  flask  was  turned  blue,  and 
the  presence  of  ammonia  was  also  shown  by  the  fumes  with  hydrochloric  acid  and  the 
reaction  with  Nessler  solution.  The  alcohol  is  boiled  off,  the  residue  taken  up  with 
ether  and  water  together,  acidified,  extracted  with  ether,  the  acids  extracted  from 
the  ether  with  a  solution  of  sodium  hydroxide,  and  the  acids  again  liberated  from  the 
alkali  by  acid  and  removed  to  the  ether  layer.  The  ether,  evaporated  spontaneously, 
left  slightly  yellowish  crusts. which  are  soluble  in  alkali,  but  insoluble  in  water.  A 
sample  of  these  crusts  when  tested  according  to  the  iodoform  reaction  gave  a  heavy 
precipitate  of  iodoform;  m.  p.,  67-70°.  The  wide  range  of  temperature  was  probably 
due  to  slight  impurities,  as  the  quantity  was  too  small  to  purify  as  much  as  desired. 
The  compound  gave  negative  qualitative  tests  for  halogen  and  nitrogen.  This  substance 
should  be  the  methyl  ketonic  acid,  aceto-camphenyl-carboxylic  acid  prepared  by  Winzer,6 
if  the  structures  of  the  preceding  compounds  are  as  stated. 

Summary 

1.  Bromonitrocamphane  on  oxidation  with  nitric  acid   breaks  down 
successively  into  camphor,  camphoric  acid  and  camphoronic  acid. 

2.  The  course  of  the  action  of  potassium  hypobromite  on  camphoroxime 
has  been  found  to  be  bromination  of  the  camphoroxime  and  then  oxida- 


11 

tion    to    the    bromonitrocamphane.     No    bromonitrocamphane    hydrate 
is  formed,  as  was  supposed  by  Forster. 

3.  Potassium  hypobromite  may  also  act  as  an  oxidizing  agent  on  cam- 
phoroxime  to  produce  hydroxy-nitrosocamphane. 

4.  Bromonitrocamphane  anhydride  has  been  prepared  by  an  improved 
method  and  the  structure  of  the  anhydride  elucidated  by  its  behavior 
with  the  Grignard  reagent,  methyl  magnesium  iodide.     Since  the  struc- 
ture of  the  anhydride  is  now  an  established  fact,  a  logical  explanation 
is  provided  by  the  unexpected  transition  from  bromonitrocamphane  to 
infra-campholenenitrile. 

5.  In  general,   this  work  fits  in  with  and  substantiates  the  work  of 
Forster  on  these  compounds. 


VITA 

The  author  was  born  on  the  7th  day  of  April,  1897,  at  Columbia,  Missouri. 
He  attended  several  grade  schools,  finishing  the  eighth  grade  at  Macomb, 
Illinois.  Then  he  entered  the  Western  Illinois  State  Teachers'  College 
Academy  and  graduated  from  there  at  the  end  of  four  years,  1911-15. 
In  the  fall  of  the  same  year,  he  entered  the  University  of  Illinois  in  the 
regular  chemistry  course,  and  graduated  with  the  B.S.  degree  in  June,  1919. 
Graduate  work  was  begun  in  the  same  University  and  the  M.S.  degree 
received  in  June,  1920.  From  that  time  to  the  present,  the  author  has  been 
doing  further  graduate  work  here. 

The  writer  taught  quantitative  chemistry  as  Graduate  Assistant  during 
the  year,  1920-21,  in  the  University  of  Illinois. 

Publications: — "Syntheses  of  Chromanes  and  Coumaranes"  Journal  of 
the  American  Chemical  Soc.,  Vol.  42,  157  (1920),  by  R.  E.  Rindfusz,  P.  M. 
Ginnings,  V.  L.  Harnack. 

Fraternities  and  Societies  :-Gammi  Pi  Upsilon,  Phi  Lambda  Upsilon, 
Associate  Member  of  Sigma  Xi,  and  American  Chemical  Society. 


Binder 
Gaylord  Bros. 

Makers 
Syracuse,  N.  Y. 

PAT.  JAN  21,  1905 


YC  2 1 545 


UNIVERSITY  OF  CALIFORNIA  LIBRARY 


